The construction and experimental verification of a 6-LncRNA model based on Lactic acid metabolism in the tumor microenvironment of Wilms tumor.

BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

lncRNA PVT1 silencing inhibits gastric cancer cells' progression via enhancing chemosensitivity to paclitaxel.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.

Triterpenes from Ganoderma lucidum inhibit hepatocellular carcinoma by regulating enhancer-associated lncRNA in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment. AIM OF THE STUDY: To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments. MATERIALS AND METHODS: Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene. RESULTS: Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells. CONCLUSIONS: Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.

LncRNA ACVR2B-as1 interacts with ALDOA to regulate the self-renewal and apoptosis of human spermatogonial stem cells by controlling glycolysis activity.

Human spermatogonial stem cells (SSCs) have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. Nevertheless, it remains unknown about the functions and mechanisms of long non-coding RNA (LncRNA) in regulating the fate determinations of human SSCs. Here we have demonstrated that LncRNA ACVR2B-as1 (activin A receptor type 2B antisense RNA 1) controls the self-renewal and apoptosis of human SSCs by interaction with ALDOA via glycolysis activity. LncRNA ACVR2B-as1 is highly expressed in human SSCs. LncRNA ACVR2B-as1 silencing suppresses the proliferation and DNA synthesis and enhances the apoptosis of human SSCs. Mechanistically, our ChIRP-MS and RIP assays revealed that ACVR2B-as1 interacted with ALDOA in human SSCs. High expression of ACVR2B-as1 enhanced the proliferation, DNA synthesis, and glycolysis of human SSCs but inhibited their apoptosis through up-regulation of ALDOA. Importantly, overexpression of ALDOA counteracted the effect of ACVR2B-as1 knockdown on the aforementioned biological processes. Collectively, these results indicate that ACVR2B-as1 interacts with ALDOA to control the self-renewal and apoptosis of human SSCs by enhancing glycolysis activity. This study is of great significance because it sheds a novel insight into molecular mechanisms underlying the fate decisions of human SSCs and it may offer innovative approaches to address the etiology of male infertility.

LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/ß-catenin signaling pathway.

OBJECTIVE: This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. METHODS: RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/ß-catenin signaling pathway. RESULTS: Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of ß-catenin (p < 0.05), p-GSK-3ß (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation. CONCLUSION: NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/ß-catenin signaling.

LncRNA XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-ß/SMAD signaling pathway.

Breast cancer is the second primary cause of cancer death among women. Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is a central regulator for X chromosome inactivation, and its abnormal expression is a primary feature of breast cancer. So far, the mechanism of XIST in breast cancer has not been fully elucidated. We attempted to illustrate the mechanism of XIST in breast cancer. The expressions of XIST, microRNA-455-3p (miR-455-3p) in breast cancer were measured using quantitative real-time PCR. The expressions of homeobox C4 (HOXC4) were assessed with immunohistochemical and Western blot. Also, the functions of XIST in breast cancer were assessed by Cell Counting Kit-8 analysis, colony formation assay, flow cytometry, Western blot, Transwell, and cell scratch assays. Meanwhile, the mechanism of XIST in breast cancer was validated using database analysis and dual-luciferase reporter assay. Furthermore, the function of XIST in breast cancer in vivo was estimated by tumor xenograft model, immunohistochemical assay, and hematoxylin-eosin staining. XIST and HOXC4 expressions were increased, but miR-455-3p expressions were decreased in breast cancer tissues and cells. Knocking down XIST restrained breast cancer cell proliferation, invasion, migration, epithelial-mesenchymal transformation (EMT), and induced cell cycle arrest at G0/G1. Meanwhile, XIST interacted with miR-455-3p, while miR-455-3p interacted with HOXC4. XIST knockdown repressed breast cancer cell proliferation, invasion, and EMT, while miR-455-3p inhibitor or HOXC4 overexpression abolished those impacts. HOXC4 overexpression also blocked the impacts of miR-455-3p mimic on breast cancer cell malignant behavior. In vivo experimental data further indicated that XIST knockdown repressed breast cancer cell tumorigenic ability, and decreased HOXC4 and p-SMAD3 (TGF-ß/SMAD-related protein) expressions.XIST/miR-455-3p/HOXC4 facilitated breast cancer development by activating the TGF-ß/SMAD pathway.

As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures.

BACKGROUND: Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. METHODS: We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model's prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. RESULTS: We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we've discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. CONCLUSION: As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.

LncRNA PKD1P6 modulates ovarian granulosa cell survival of hyperandrogenic polycystic ovary syndrome by targeting miR-135b-5p and inhibiting ERK1/2 signaling.

Polycystic ovary syndrome (PCOS) is the most common and multifactorial endocrine disease among women of reproductive age. Aberrant folliculogenesis is a common pathological characteristic of PCOS, but the underlying molecular mechanism remains unclear. Emerging evidence indicated that aberrant expression of long noncoding RNAs (lncRNAs) may contribute to the pathogenesis of PCOS. In this study, we found that lncRNA PKD1P6 expression was remarkably down-regulated in ovarian granulosa cells (GCs) of hyperandrogenic PCOS (HA-PCOS) patients and negatively correlated with serum testosterone (T) levels. We further showed that overexpression of PKD1P6 markedly reduced cell viability, attenuated DNA synthesis capacity, arrested the cell cycle at G0/G1 phase and promoted apoptosis of KGN cells. Exosomes derived from PKD1P6 overexpression cells exerted similar effects to PKD1P6 overexpression on the function of KGN cells. Mechanistically, PKD1P6 could act as a competing endogenous RNA (ceRNA) by directly binding with miR-135b-5p. Overexpression of PKD1P6 significantly suppressed ERK1/2 activation, whereas up-regulation of miR-135b-5p exerted an opposing effect. Additionally, excessive androgen was showed to diminish PKD1P6 expression while promote miR-135b-5p expression of PCOS models in vitro and vivo. Collectively, our findings delineate the clinical significance of PKD1P6 in HA-PCOS and the new regulatory mechanisms involved in abnormal folliculogenesis, providing a promising therapeutic target for HA-PCOS.

Current insights and future directions of LncRNA Morrbid in disease pathogenesis.

Non-coding RNAs have emerged as important regulators of gene expression and contributors to many diseases. LncRNA Morrbid, a long non-coding RNA, has been widely studied in recent years. Current literature reports that lncRNA Morrbid is involved in various diseases such as tumors, cardiovascular diseases, inflammatory diseases and metabolic disorder. However, controversial conclusions exist in current studies. As a potential therapeutic target, it is necessary to comprehensively review the current evidence. In this work, we carefully review the literature on Morrbid and discuss each of the hot topics related to lncRNA Morrbid.

Clinical Significance of the Expression of Long Non-Coding RNA LINC01508 in Non-Small Cell Lung Cancer.

The expression of long non-coding RNA (lncRNA) LINC01508 was studied in tumor samples from patients with non-small cell lung cancer (NSCLC), and its clinical significance was evaluated. The expression of LINC01508 lncRNA was measured in 16 pairs of NSCLC samples and its association with clinical and morphological features of the disease and prognosis analyzed. A comparative analysis showed a significant decrease in the expression of LINC01508 in tumor lung tissue in comparison with the surrounding normal lung tissue. The informativity of the diagnostic method was tested using ROC curve analysis and calculation of the area under the curve (AUC) for LINC01508 in NSCLC patients, which showed an AUC of 0.875 (p=0.001). No significant associations of LINC01508 expression level with clinical and morphological characteristics of the disease were found. The analysis of prognostic significance showed that high expression of LINC01508 in NSCLC samples was a favorable prognostic factor. Despite the fact that the results did not reach statistical significance (p=0.107), the median survival rate for patients with low LINC01508 expression was 16 months, while for patients with high expression, it was not reached during the follow-up period. We believe that LINC01508 can be a promising independent prognostic marker for NSCLC.

LncRNA 51A: A promising diagnostic biomarker for assessing cognitive decline in occupationally exposed aluminum workers.

OBJECTIVE: To assess the diagnostic utility of lncRNA 51 A in detecting cognitive decline among aluminum-exposed workers occupationally. METHODS: 921 male workers from an aluminum manufacturing facility underwent cognitive assessments, measurement of plasma aluminum levels and quantification of lncRNA 51 A levels. Receiver Operating Characteristic (ROC) curves were constructed to assess the diagnostic potential of lncRNA 51 A. Bayesian network model was utilized to predict the likelihood of cognitive decline among the study population. RESULTS: Significant differences in lncRNA 51 A levels, plasma aluminum concentration and MMSE scores were observed between cognitive normal and decline groups. The lncRNA 51 A expression was negatively correlated with MMSE scores. The area under the curve (AUC) was 0.894, with 89.3 % sensitivity and 73.9 % specificity. The Bayesian network model indicated varying probabilities of cognitive decline based on lncRNA 51 A expression levels. CONCLUSION: Plasma lncRNA 51 A shows potential as an excellent biomarker for cognitive decline diagnosis in aluminum-exposed workers.

Alteration of lncRNA RHPN1-AS1 predicts clinical prognosis and regulates the progression of bladder cancer via modulating miR-485-5p.

BACKGROUND: Exploring effect biomarkers that monitor tumor progression and predict the prognosis could benefit the clinical management of bladder cancer and improve the postoperative life of patients. This study aimed to estimate the function of long non-coding (lnc)RNA RHPN1-AS1 (RHPN1-AS1) in bladder cancer and the potential molecular mechanism. METHODS: The expression of RHPN1-AS1 was evaluated in bladder cancer tissues from 115 patients and cells by polymerase chain reaction. The clinical significance of RHPN1-AS1 was assessed and its effect was also estimated in cell proliferation, migration, and invasion. The underlying molecular mechanism was explored by the dual-luciferase reporter assay. RESULTS: The expression of RHPN1-AS1 was 2.91-fold elevated in bladder cancer, which showed a close correlation with advanced tumor node metastasis stage (P = 0.013) and the presence of lymph node metastasis (P = 0.018). RHPN1-AS1 also served as a poor prognostic indicator (hazard ratio = 2.563) for bladder cancer. The knockdown of RHPN1-AS1 significantly suppressed the proliferation and metastasis ability of bladder cancer cells. Moreover, miR-485-5p was found to mediate the function of RHPN1-AS1 in bladder cancer, which was considered the underlying regulatory mechanism. CONCLUSIONS: RHPN1-AS1 serves as a prognostic biomarker and tumor promoter in bladder cancer via modulating miR-485-5p, which might be a reliable target of bladder cancer therapy.

Role of the lncRNA/Wnt signaling pathway in digestive system cancer: a literature review.

The long noncoding RNA (lncRNA)/Wingless (Wnt) axis is often dysregulated in digestive system tumors impacting critical cellular processes. Abnormal expression of specific Wnt-related lncRNAs such as LINC01606 (promotes motility), SLCO4A1-AS1 (promotes motility), and SH3BP5-AS1 (induces chemoresistance), plays a crucial role in these malignancies. These lncRNAs are promising targets for cancer diagnosis and therapy, offering new treatment perspectives. The lncRNAs, NEF and GASL1, differentially expressed in plasma show diagnostic potential for esophageal squamous cell carcinoma and gastric cancer, respectively. Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.

Current knowledge of antisense long non-coding RNA in the occurrence and prognosis of skull base tumors.

Antisense long non-coding RNA (AS-lncRNA) represents a novel class of RNA molecules. In recent years, it has been discovered that AS-lncRNAs play crucial roles in various biological processes, particularly in the onset and progression of tumors. Skull base tumors, originating from the base of the brain, exhibit specific expression patterns of AS-lncRNA which correlate significantly with clinical characteristics. This makes AS-lncRNA a promising candidate as a tumor marker. Functional studies have revealed that AS-lncRNAs can regulate gene expression by acting as miRNA sponges and interacting with RBPs. Consequently, they play pivotal roles in tumor cell cycle, apoptosis, angiogenesis, invasion, and metastasis processes. Further exploration into the mechanisms of AS-lncRNA in tumors holds substantial theoretical significance for deeper insights into the etiology, pathogenesis, and RNA dynamics of skull base tumors. Moreover, AS-lncRNA could serve as molecular markers or potential targets for early diagnosis. Their potential extends to efficacy assessment, prognosis prediction, and gene therapy, suggesting broad clinical applications. In summary, AS-lncRNA emerges as a promising molecular marker implicated in the onset and progression of skull base tumors.

The prognostic significance of lncRNA FGD5-AS1 in various malignancies: a meta-analysis.

Background: Cancer is widely recognized as a prominent contributor to global mortality due to factors such as delayed diagnosis, unfavorable prognosis, and high likelihood of recurrence. FGD5 transcription factor G antisense RNA 1(FGD5-AS1), a newly identified long non-coding RNA, has emerged as a promising prognostic biomarker, for malignancy prognosis. This meta-analysis aimed to assess the prognostic significance of FGD5-AS1 in various carcinomas. Methods: A systematic search was performed through five electronic databases to identify studies that investigating the role of FGD5-AS1 expression as a prognostic factor in carcinomas. The value of FGD5-AS1 in malignancies was estimated by odds ratios (ORs) and hazard ratios (HRs) with a corresponding 95% confidence intervals (CIs). Furthermore, the GEPIA database was used to further supplement our results. Results: This analysis included 12 studies with 642 cases covering eight cancer types. High FGD5-AS1 expression exhibited a significant correlation with poor overall survival(OS) (HR = 2.04, 95%CI [1.72, 2.42], P < 0.00001), advanced tumor stage (OR = 3.47, 95%CI [2.34, 5.14], P < 0.00001), lymph node metastasis(LNM) (OR = 1.79, 95% CI [1.20,2.67], P = 0.004), and larger tumor size (OR= 5.25, 95%CI [2.68, 10.30], P < 0.00001). Furthermore, the FGD5-AS1 expression was notably upregulated in six types of malignancies as verified using the GEPIA online gene analysis tool. Conclusions: The findings of this meta-analysis indicated that high FGD5-AS1 expression was significantly associated with poor prognosis in diverse cancer types, suggesting that FGD5-AS1 may be a promising biomarker for predicting cancer prognosis. Systematic review registration: https://www.york.ac.uk/inst/crd, identifier CRD42024552582.

lncRNA H19 facilitates vascular neointima formation by targeting miR-125a-3p/FLT1 axis.

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.

Identification of lysine lactylation (kla)-related lncRNA signatures using XGBoost to predict prognosis and immune microenvironment in breast cancer patients.

Breast cancer (BC) stands as a predominant global malignancy, significantly contributing to female mortality. Recently uncovered, histone lysine lactylation (kla) has assumed a crucial role in cancer progression. However, the correlation with lncRNAs remains ambiguous. Scrutinizing lncRNAs associated with Kla not only improves clinical breast cancer management but also establishes a groundwork for antitumor drug development. We procured breast tissue samples, encompassing both normal and cancerous specimens, from The Cancer Genome Atlas (TCGA) database. Utilizing Cox regression and XGBoost methods, we developed a prognostic model using identified kla-related lncRNAs. The model's predictive efficacy underwent validation across training, testing, and the overall cohort. Functional analysis concerning kla-related lncRNAs ensued. We identified and screened 8 kla-related lncRNAs to formulate the risk model. Pathway analysis disclosed the connection between immune-related pathways and the risk model of kla-related lncRNAs. Significantly, the risk scores exhibited a correlation with both immune cell infiltration and immune function, indicating a clear association. Noteworthy is the observation that patients with elevated risk scores demonstrated an increased tumor mutation burden (TMB) and decreased tumor immune dysfunction and exclusion (TIDE) scores, suggesting heightened responses to immune checkpoint blockade. Our study uncovers a potential link between Kla-related lncRNAs and BC, providing innovative therapeutic guidelines for BC management.

Cuproptosis-associated lncRNA impact prognosis in patients with non-small cell lung cancer co-infected with COVID-19.

Non-small cell lung cancer (NSCLC) patients infected with COVID-19 experience much worse prognosis. However, the specific mechanisms behind this phenomenon remain unclear. We conducted a multicentre study, collecting surgical tissue samples from a total of 36 NSCLC patients across three centres to analyse. Among the 36 lung cancer patients, 9 were infected with COVID-19. COVID-19 infection (HR = 21.62 [1.58, 296.06], p = 0.021) was an independent risk factor of progression-free survival (PFS). Analysis of RNA-seq data of these cancer tissues demonstrated significantly higher expression levels of cuproptosis-associated genes in COVID-19-infected lung cancer patients. Using Lasso regression and Cox regression analysis, we identified 12 long noncoding RNAs (lncRNA) regulating cuproptosis. A score based on these lncRNA were used to divide patients into high-risk and low-risk groups. The results showed that the high-risk group had lower overall survival and PFS compared to the low-risk group. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) database revealed that the high-risk group benefited more from immunotherapy. Drug sensitivity analysis identified cetuximab and gefitinib as potentially effective treatments for the high-risk group. Cuproptosis plays a significant role NSCLC patients infected with COVID-19. Promisingly, cetuximab and gefitinib have shown potential effectiveness for managing these patients.

Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ.

MicroRNAs (miRNAs) play crucial roles in physiological functions and disease, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, reveals its proximity to splicing factor proline- and glutamine (Q)-rich (SFPQ), a multifunctional RNA-binding protein (RBP) involved in forming paraspeckle nuclear condensates. SFPQ depletion impacts both primary and mature miRNA expression, while other paraspeckle proteins (PSPs) or the paraspeckle scaffolding RNA NEAT1 do not, indicating a paraspeckle-independent role. Comprehensive transcriptomic analyses show that SFPQ loss broadly affects RNAs and miRNA host gene (HG) expression, influencing both their transcription and the stability of their products. Notably, SFPQ protects the oncogenic miR-17∼92 polycistron from degradation by the nuclear exosome targeting (NEXT)-exosome complex and is tightly linked with its overexpression across a broad variety of cancers. Our findings reveal a dual role for SFPQ in regulating miRNA HG transcription and stability, as well as its significance in cancers.

A multispecies study reveals the diversity and potential regulatory role of long noncoding RNAs in cucurbits.

Plant long noncoding RNAs (lncRNAs) exhibit features such as tissue-specific expression, spatiotemporal regulation, and stress responsiveness. Although diverse studies support the regulatory role of lncRNAs in model plants, our knowledge about lncRNAs in crops is limited. We employ a custom pipeline on a dataset of over 1000 RNA-seq samples across nine representative species of the family Cucurbitaceae to predict 91 209 nonredundant lncRNAs. The lncRNAs were characterized according to three confidence levels and classified by their genomic context into intergenic, natural antisense, intronic, and sense-overlapping. Compared with protein-coding genes, lncRNAs were, on average, expressed at low levels and displayed significantly higher specificity when considering tissue, developmental stages, and stress responsiveness. The evolutionary analysis indicates higher positional conservation than sequence conservation, probably linked to the conserved modular motifs within syntenic lncRNAs. Moreover, a positive correlation between the expression of intergenic/natural antisense lncRNAs and their closest/parental gene was observed. For those intergenic, the correlation decreases with the distance to the neighboring gene, supporting that their potential cis-regulatory effect is within a short-range. Furthermore, the analysis of developmental studies showed that a conserved NAT-lncRNA family is differentially expressed in a coordinated way with their cognate sense protein-coding genes. These genes code for proteins associated with phloem development, thus providing insights about the potential involvement of some of the identified lncRNAs in a developmental process. We expect that this extensive inventory will constitute a valuable resource for further research lines focused on elucidating the regulatory mechanisms mediated by lncRNAs in cucurbits.